Aminopyrimidinyl compounds

Abstract

A compound compound having the structure: or a pharmaceutically acceptable salt thereof, wherein X is N or CR, where R is hydrogen, deuterium, C-Calkyl, C-Calkoxy, C-Ccycloalkyl, aryl, heteroaryl, aryl(C-Calkyl), CN, amino, alkylamino, dialkylamino, CF, or hydroxyl; A is selected from the group consisting of a bond, C═O, —SO—, —(C═O)NR—, and —(CRR)—, where Ris H or C-Calkyl, and Rand Rare independently hydrogen, deuterium, C-Calkyl, C-Ccycloalkyl, aryl, aryl(C-Calkyl), heteroaryl, (C-Calkyl)heteroaryl, etc.; A' is selected from the group consisting of a bond, C═O, —SO—, —(C═O)NR′, —NR′(C═O)—, and —(CR′R′)—, where R′ is H or C-Calkyl, and R′ and R′ are independently hydrogen, deuterium, C-Calkyl, C-Ccycloalkyl, aryl, aryl(C-Calkyl), heteroaryl, (C-Calkyl)heteroaryl, heteroaryl(C-Calkyl), and heterocyclic(C-Calkyl); Z is —(CH)— or a bond, where one or more methylene units are optionally substituted by one or more C-Calkyl, CN, OH, methoxy, or halo, and where said alkyl may be substituted by one or more fluorine atoms; Rand R′ are independently selected from the group consisting of hydrogen, deuterium, C-Calkyl, C-Ccycloalkyl, aryl, heteroaryl, aryl(C-Calkyl), CN, etc., wherein said alkyl, aryl, cycloalkyl, heterocyclic, or heteroaryl is further optionally substituted with one or more substituents selected from the group consisting of C-Calkyl, halo, CN, C-Calkylamino, C-Ccycloalkyl, etc.; Ris selected from the group consisting of hydrogen, deuterium, C-Calkyl, C-Ccycloalkyl, halo, and cyano, where said alkyl may be substituted by one or more fluorine atoms; Ris selected from the group consisting of hydrogen, deuterium, and amino; Ris monocyclic or bicyclic aryl or monocyclic or bicyclic heteroaryl wherein said aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of C-Calkyl, heterocycloalkyl, halo, C-Ccycloalkyl, etc., where said alkyl, cycloalkyl, alkoxy, or heterocycloalkyl may be substituted by one or more C-Calkyl, halo, CN, OH, alkoxy, amino, —COH, —(CO)NH, —(CO)NH(C-Calkyl), or —(CO)N(C-Calkyl), and where said alkyl may be further substituted by one or more fluorine atoms; Ris independently selected from the group consisting of hydrogen, C-Calkyl, C-Calkoxy, and hydroxyl; h is 1, 2 or 3; j and k are independently 0, 1, 2, or 3; m and n are independently 0, 1 or 2; and, q is 0, 1 or 2. Also provided are methods of treatment as Janus Kinase inhibitors and pharmaceutical compositions containing the compounds of the invention and combinations with other therapeutic agents.